title: Heterogeneous pattern of renal disease associated with homozygous factor H deficiency.
abstract: Membranoproliferative glomerulonephritis type II is a rare renal disease, associated with uncontrolled activation of the complement alternative pathway because of C3 nephritic factor. Abnormalities in factor H have been rarely described in patients with membranoproliferative glomerulonephritis type II. We report the clinical history, molecular defect, and histologic description of 3 patients with factor H deficiency and various types of membranoproliferative glomerulonephritis. The 3 patients presented with severely decreased C3. Circulating factor H was undetectable. Complete factor H deficiency (CFH) was due to homozygous complement factor H mutations in short consesus repeat (SCR) 7, 10, and 11. Age at onset was 1 (patient 1), 17 (patient 2), and 33 years (patient 3). Symptoms at diagnosis included proteinuria of 0.5, 2.4, and 11 g/d, respectively, microhematuria, and normal renal function in all cases. The estimated glomerular filtration rate at last follow-up was 25, 43, and 112 mL/min per 1.73 m(2), at ages of 29, 24, and 37 years, respectively. Renal biopsies disclosed a membranoproliferative glomerulonephritis type II with atypical discontinuous dense deposits in patient 1; a membranoproliferative glomerulonephritis type I with immunoglobin G (IgG), C1q, and abundant C3 deposits in patient 2; and a membranoproliferative glomerulonephritis with isolated C3 deposits without dense deposits in patient 3. This report of factor H-deficient patients emphasizes the diversity of the histologic lesions associated with factor H deficiencies and the role of the alternative pathway in several subtypes of membranoproliferative glomerulonephritis.
authors.affiliation: Department of Nephrology, Hôpital Necker-Enfants Malades AP-HP, Paris 75015, France. aude.servais@nck.aphp.fr
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Dragon-Durey
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gübler
authors.forename: Philippe
authors.initials: P
authors.lastname: Rémy
authors.forename: David
authors.initials: D
authors.lastname: Buob
authors.forename: Carole
authors.initials: C
authors.lastname: Cordonnier
authors.forename: Raïfah
authors.initials: R
authors.lastname: Makdassi
authors.forename: Waddah
authors.initials: W
authors.lastname: Jaber
authors.forename: Eric
authors.initials: E
authors.lastname: Boulanger
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesavre
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003178:Complement C3 Nephritic Factor / Q000235:genetics; D017242:Complement Factor H / Q000172:deficiency*; D003170:Complement Pathway, Alternative / Q000235:genetics; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male
chemical_list: D003178:Complement C3 Nephritic Factor; D017242:Complement Factor H